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2019, Volume 35, Number 1, Page(s) 052-054
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DOI: 10.5146/tjpath.2016.01370 |
Primary Clear Cell Renal Cell Carcinoma with Marked Intraluminal Mucin Secretion |
Oğuzhan OKCU1, Kemal BEHZATOĞLU1, Yasemin ÇAKIR1, Esra PAŞAOĞLU2, Uğur YÜCETAŞ3 |
1Department of Pathology, Istanbul Education and Research Hospital, İstanbul, Turkey 2Bagcılar Education and Research Hospital, İstanbul, Turkey 3Department of Urology, Istanbul Education and Research Hospital, İstanbul, Turkey |
Keywords: Clear cell renal cell carcinoma, Mucin |
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Clear cell renal cell carcinoma with mucin secretion is an unexpected situation. Primary renal adenocarcinoma and various metastatic carcinomas
should be considered in the differential diagnosis. Prognostic significance is not yet fully known due to the limited number of reported cases,
and these lesions have been grouped under unclassified renal cell carcinoma. In our study, clear cell renal cell carcinoma with significant luminal
mucin secretion is discussed with its histological, histochemical and immunohistochemical features. |
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Mucins are complex carbohydrates secreted by epithelial
and connective tissues. They are secreted by normal cells
of endodermal origin such as gastric, intestinal, pancreatic,
prostatic and pulmonary cells 1-3. Mucin secretion
increases in adenocarcinomas of these organs, and sometimes
gastrointestinal system and breast adenocarcinomas can be
named “mucinous adenocarcinoma' when there is excessive
extracellular mucin secretion. The presence of mucin
in the gland is also a feature supporting the diagnosis of
prostate carcinoma. Similarly, it is important to determine
mucin secretion in the diagnosis and differential diagnosis
of adenocarcinoma metastases from this organ. Mucin
presence in the gland is an unexpected feature and very rare
in renal cell carcinomas and especially in the common clear
cell type. Only two cases have been reported in the English
literature so far 4,5.
Renal adult tumors that show significant extracellular
mucin production are mucinous tubular and spindle
cell carcinoma, oncocytoma, tubulo-papillary adenoma,
collecting duct carcinoma, papillary renal cell carcinoma
(RCC), tubulocystic carcinoma, and renal medullary
carcinoma 4,6. However, extracellular (intraluminal)
mucin expression is quite rare in clear cell RCC. RCC is
therefore not considered in the presence of intraluminal
mucin in metastatic carcinomas of unknown origin. Clear
cell RCC's with mucin secretion have not been defined in
the most recent Vancouver classification and are generally
evaluated within the unclassified RCC classification 7.
We discuss the histological, histochemical and
immunohistochemical features and the problems related to
differential diagnosis presented by a conventional renal cell
carcinoma case with extensive luminal mucin secretion. |
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Abstract
Introduction
Case Presentation
Disscussion
References
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A 71-year-old male with no symptoms was incidentally
found to have a 5 cm mass in the right kidney upper pole with
abdominal ultrasonography during a routine examination
(check-up). CT imaging showed no evidence of abdominal
or retroperitoneal lymphadenopathy, organomegaly or
distant metastasis. Right radical nephrectomy was therefore
performed by the urology department.
On macroscopic evaluation, there was a nodular, welldelineated
tumoral lesion 5 cm in size, located in the upper
pole of the nephrectomy material measuring 11x8x5 cm.
The tumor was yellow-brown, while occasional areas had a
more shiny appearance. Hemorrhage in focal areas was also
observed. The tumor infiltrated the hilus fatty tissue.
Microscopic evaluation revealed that the tumor contained
alveolar nests containing cells with a clear cytoplasm,
prominent cytoplasmic borders and a glandular pattern.
The nuclei in these clear cell areas had features of Fuhrman
grade II. The cytoplasm was eosinophilic-granular and the
nuclei were slightly larger in some areas (Fuhrman grade
III). There was a definite distinction between the areas
with a granular cytoplasm and clear cytoplasm (Figure 1).
The most interesting feature of the areas with a granular
cytoplasm was the blue-colored mucin-like material filling
the gland lumens (Figure 2,3).
 Click Here to Zoom |
Figure 1: Definite distinction between the areas with a granular
cytoplasm and clear cytoplasm (H&E; x40). |
 Click Here to Zoom |
Figure 2: Glandular structures with eosinophilic cytoplasm and
high-grade nuclear features, containing mucin in the lumen
(H&E; x200). |
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Figure 3: Glandular structures with eosinophilic cytoplasm and
high-grade nuclear features, containing mucin in the lumen
(H&E; x100). |
The mucin-like material stained dark rose with mucicarmen
and blue with PAS-Alcian blue (Figure 4) pH 2.5, while
intracytoplasmic staining was only observed in a few cells
on histochemical staining.
 Click Here to Zoom |
Figure 4: Alcian blue positivity in glandular structures (Alcien-
Blue; x100). |
Immunohistochemical studies revealed that all cells with
clear and granular cytoplasm were positive for PAX-8 and
CD10 but negative for vimentin and cytokeratin (CK)
7. The case was diagnosed as “clear renal cell carcinoma
with marked intraluminal mucin secretion”. The patient is
alive after 74 months of follow-up without any evidence of
recurrence. |
Top
Abstract
Introduction
Case Presentation
Disscussion
References
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The kidney is derived from the mesoderm and intestinal
type mucin expression in its carcinomas is an unexpected
feature. This is not a commonly expected feature of RCC,
the most frequent tumor of the kidney.
The presence of mucin in the tubule in RCC makes
diagnosis of the primary tumor more difficult and can create
significant problems in metastatic cases. Mucin presence in
metastasis is not a feature indicating RCC. Only two cases
with intraluminal mucin secretion in clear cell RCC have been reported so far 4,5. In our case, mucin was present
in a primary clear cell RCC; the typical clear cell areas and
immunohistochemically diffuse PAX8 and CD10 positivity
and CK7 negativity helped in making the diagnosis.
CK20, TT F-1, PSA, GATA-3 can be added to the immune
panel in order to distinguish primary renal carcinoma
from colonic, pulmonary, prostatic, urothelial carcinoma
metastases whenever mucin is seen in the tumor. Although
mucin secretion is more frequently seen in mucinous and
spindle cell carcinoma, Pivovarcikova et al. reported 7
cases of papillary RCC with extracellular and intracellular
mucin secretion 6. Transition of cord-like structures to
spindle cells and myxoid stroma in mucinous and spindle
cell carcinoma, and presence of papillary structures in
papillary RCC are important morphological features for
distinction from clear cell RCC with mucin secretion 6.
Absence of papillary structures, spindle cells and stromal
mucin as well as presence of typical morphological
features of clear cell RCC and CK7 negativity aided in the
diagnosis. However, cases consisting of cells with complete
eosinophilic cytoplasm and containing diffuse mucin
may create diagnostic problems. The intraluminal mucin
secretion in our case is a quite noteworthy feature of clear
cell RCC. Similar histological features were present in two
cases published previously 4,5. Our case had similar
histology but we also noted areas containing cells with a
dense eosinophilic cytoplasm with intraluminal mucin and
high nuclear grade with distinct borders. These mucincontaining
areas may have developed a different molecular
characteristic compared to the clear cell areas. It is
interesting that the three cases presented with high nuclear
grade (Fuhrman Grade: III) and advanced stage (all pT3)
despite the lack of recurrence or metastasis during followup.
This indicates the possibility of a high metastasis rate in
these cases and the need for more careful clinical follow-up.
In addition to the WHO 2004 classification, the
International Society of Urological Pathology (ISU P) has
added many new entities to RCC in its Vancouver (2012)
meeting 7,8. This new entity was also added in the last
WHO classification 9. This new classification includes
tubulocystic RCC, RCC related to acquired cystic disease,
clear cell (tubulo) papillary RCC, MIT family translocation
carcinoma and hereditary leiomyomatosis RCC and
related RCC entities in addition to clear cell, papillary and
chromophobe RCC. All of these entities have been defined
as new entities in the most recent WHO 2016 classification
9. Clear cell RCC with significant mucin secretion has
not been considered in the Vancouver consensus meeting
and the most recent WHO classification. The presence of very few cases so far may have played a role. This entity
will probably continue to be included in the unclassified
group for now. New case reports are needed to determine
if this entity has any prognostic significance besides the
morphological differences.
In conclusion, we believe intraluminal mucin production in
renal cell carcinoma is an entity that should be considered
despite its rarity. Differentiation of clear cell renal cell
carcinoma with mucin secretion from the renal metastasis
of mucin-secreting tumors is also important. One must
remember that mucin production of the tumor in primary
and metastatic foci will not exclude renal cell carcinoma.
CONFLICT OF INTERESTS
The authors declared no conflict of interest. |
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Abstract
Introduction
Case Presentation
Discussion
References
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1) S ingh AP, Moniaux N, Chauhan SC, Meza JL, Batra SK . Inhibition
of MUC4 expression suppresses pancreatic tumor cell growth and
metastasis. Cancer Res. 2004;64: 622-30.
2) Hakomori S. Aberrant glycosylation in tumors and tumorassociated
carbohydrate antigens. Adv Cancer Res. 1989;52: 257-331.
3) N iv Y. Mucin and colorectal cancer metastasis. Am J Gaslroenterol.
1994;89:665-9.
4) Val-Bernal JF, Salcedo W, Val D, Parra A, Garijo MF. Mucinsecreting
clear cell renal cell carcinoma. A rare variant of
conventional renal cell carcinoma. Annal Diagn Pathol. 2013;17:
226–9.
5) R aheem OA, Godebu E, Cohen SA, Shabaik A, Parsons
JK. Unclassified mucinous renal cell carcinoma: A rare
histopathological entity. Korean J Urol. 2014;55:690-2.
6) Pivovarcikova K, Peckova K, Martinek P, Montiel DP, Kalusova
K, Pitra T, Hora M, Skenderi F, Ulamec M, Daum O, Rotterova
P, Ondic O, Dubova M, Curik R, Dunatov A, Svoboda T, Michal
M, Hes O. Mucin secreting papillary renal cell carcinoma:
Clinicopathological, immunohistochemical, and molecular
genetic analysis of seven cases. Virchows Arch. 2016; 469: 71-80.
7) Ozagari AA. Recommendations from the 2012 International
Society of Urological Pathology Vancouver Consensus Conference
on Renal Tumors. Bulletin of Urooncology. 2015;14:285-9.
8) Eble JN, Sauter G, Epstein JI, Sesterhenn IA. Pathology and
genetics of the tumours of the urinary system and male genital
organs. Lyon: IARC; 2004.
9) Moch H, Humphrey PA, Ulbright TM, Reuter VE. WHO
Classification of Tumors of the Urinary System and Male genital
organs. Lyon: IARC; 2016. |
Top
Abstract
Introduction
Case Presentation
Discussion
References
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